Les "mauvaises pratiques" chromatographiques ciblées par l'US FDA...
Plusieurs "Warning Letter" récentes mettent en évidence des observations sur l'utilisation des systèmes de gestion de données chromatographiques ; dans la première, la sécurisation des méthodes et paramètres d'intégration est mise en cause :
b. Chromatographic test methods do not have established integration parameters, and analysts are permitted to(b)(4)In your response, you state that integration parameters and processing methods will be secured so that all data is processed with the same processing method. Your response to this observation will be evaluated at the next routine inspection of your facility; however, it is important to note this is a repeat observation from the January 2011 inspection.
1. We observed and documented practices during the inspection that (you) kept some samples, data and results outside of the local systems for assessing quality. This raises serious concerns regarding the integrity and reliability of the data generated at your Kalyani plant. For example,
a. Our review of the Chromeleon and Empower II software found that your firm was testing samples unofficially, and not reporting all results obtained. Specifically, “test,” “trial” and “demo” injections of intermediate and final API samples were performed, prior to performing the tests that would be reported as the final QC results.
b. Out-of-specification or undesirable results were ignored and not investigated.
c. Samples were retested without a record of the reason for the retest or an investigation. Only passing results were considered valid, and were used to release batches of APIs intended for US distribution.
d. Unacceptable practices in the management of electronic data were also noted. The management of electronic data permitted unauthorized changes, as digital computer folders and files could be easily altered or deleted...
3. Your laboratory control records do not include data derived from all of the tests necessary to establish compliance with standards.
For example, the inspection found multiple raw data chromatograms in digital files labeled “test” and “demo,” that were injected prior to the sample injections that were used to conclude that batches were in conformance with the specification...
Enfin dans la troisième :
3. Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to assure compliance with established specifications and standards (21 CFR 211.194(a)).
For example, your firm’s laboratory records failed to include complete records of all stability testing performed. The FDA investigators identified the practice of performing "trial" sample analysis for High Performance Liquid Chromatography (HPLC) analyses prior to collecting the “official” analytical data for stability testing. These “trials” were performed on multiple products, including (b)(4) Tablets (b)(4)mg, (b)(4)mg/(b)(4)ml, and (b)(4)Tablets. These trial runs were not recorded in the equipment use log, and sample preparation data associated with these analyses was destroyed, preventing any calculation or analysis of the resulting data. Your response states that trial runs were conducted using only one of the (b)(4) HPLC instruments located in the stability laboratory, which happened to be the one instrument that the FDA investigators reviewed during the inspection. Your response indicates that you have revised procedures and re-trained your staff.
Additionally, your quality control HPLC raw data files can be deleted from the hard drive using the common PC login used by all (b)(4) analysts. This deletion eliminates all records of sample injections and analyses. Your response indicates that this deletion function is only available on the software used for one of (b)(4) sets of HPLC instruments. You also indicated that you have changed the access control privileges such that laboratory analysts in a “user” role cannot delete or rename files.
